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Title page for ETD etd-09242014-104555


Type of Document Dissertation
Author Sullivan, Chelsea Suzanne
URN etd-09242014-104555
Title The mechanisms by which apoptotic neurons in the developing dorsal root ganglia are engulfed
Degree PhD
Department Biochemistry
Advisory Committee
Advisor Name Title
Bruce Carter Committee Chair
Alyssa Hasty Committee Member
David Cortez Committee Member
Luc Van Kaer Committee Member
Scott Hiebert Committee Member
Keywords
  • autoimmunity
  • satellite glial cells
  • engulfment
  • efferocytosis
Date of Defense 2014-08-29
Availability unrestricted
Abstract
During development of the nervous system, approximately 50% of the neurons generated undergo apoptosis as part of a normal pruning process. The neuronal corpses must be efficiently cleared to prevent an immune system response. We demonstrated that satellite glial precursor cells are the main phagocytes in the developing dorsal root ganglia (DRG), and identified a novel engulfment receptor necessary for this engulfment, Jedi-1. Jedi-1 contains immunoreceptor tyrosine based activation motifs (ITAMs) that bind to the tyrosine kinase Syk, which is required for phagocytosis. Jedi-1 also contains an NPXY motif that is required for interaction with the adapter protein GULP, which was also necessary for engulfment. Jedi-1 associates with GULP and recruits clathrin heavy chain (CHC), which promotes actin rearrangement required for engulfment. To determine the role of Jedi-1 in vivo we generated jedi-1 -/- mice. Apoptotic neurons accumulate in the developing DRG of jedi-1 -/- mice, and the mice develop autoimmune disease including the production of autoantibodies and kidney dysfunction. The jedi-1 null mice also exhibit excessive itching which results in skin lesions. Our data suggests that this itch phenotype may be due to activation of satellite glial cells in response to defective clearance of apoptotic neurons.
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